1. Technical Field
The present invention relates to a bacteriophage MPK6 and a progeny bacteriophage thereof, and a pharmaceutical composition for treating a Pseudomonas aeruginosa infection disease.
2. Background Art
Pseudomonas aeruginosa is an opportunistic human pathogen that is ubiquitously found in various biotic and abiotic environments. It is frequently isolated from human patients afflicted with cystic fibrosis, otitis media, kertatitis, and burn wound infections, as an etiological agent of septicemia in immunocompromised individuals. This bacterium, generally from the environmental reservoir, can colonize a large numbers of child patients before the age of 3 years, and adversely affect their pulmonary function (28, 33). Furthermore, P. aeruginosa is also commonly found in peritonitis-sepsis cases secondary to ruptured appendices in otherwise healthy children (4). Peritonitis by P. aeruginosa is a serious threat also to the patients undergoing continuos ambulatory peritoneal dialysis (CAPD) (17), accounting for 10% of fatality cases associated with CAPD. The bacterial intoxication usually leads to high morbidity, CAPD failure, and late complications in those cases (16, 17, 19). Rodent models of P. aeruginosa peritonitis have been developed for understanding the pathophysiology implicated in peritonitis (38). The pathological consequences generally accompany bacteremia and infected livers with serum levels of interleukin-6 elevated within 6 h post-infection and ultimately cause mortality within 48 hours depending on P. aeruginosa strains and infection doses (5).
Although antibiotics have still been widely used to control the bacterial infections, they are more frequently ineffective due to the inevitable emergence of antibiotic resistance. Selection and dissemination of intrinsic and acquired antibiotic resistance mechanisms increase the proclivity to resist the chemotherapy involving various antibiotics and promote the emergence of bacterial strains with multiple antibiotic resistances, which are associated with the mortality and morbidity in infected patients nowadays (26, 34). Hence, development of new therapeutic and prophylactic strategies is compulsory in the control of the bacterial infections.
As an alternative and/or supplementary antiinfective modality for combating infections caused by antibiotic-resistant microorganisms, which is currently being revisited in various countries, is bacteriophages that are able to specifically target their host bacterial infections, which is called phage therapy (35). Phage therapy is a method of harnessing phages as bioagents and was first introduced by Felix d'Herelle back in 1916, before the discovery of the first antibiotic, penicillin (36). Phages continue to be used in place of antibiotics for the treatment of bacterial infections in the former Soviet Union and the Eastern Europe (30). Much more attention has recently been paid to phage therapy, as more and more bacteria have very rapidly evolved antibiotic resistance. Thus phage therapy may be a valuable alternative modality to antibiotics and has already been proven to be medically superior to antibiotics in certain cases (3, 22).
P. aeruginosa is a highly adaptable bacterium that enhances its ecological fitness even in the presence of conventional antibiotic therapy. The rapid emergence of new P. aeruginosa strains as well as the persistence of the existing antibiotic-resistant clinical isolates has led to an urgent need to explore more sustainable alternative strategies such as phage therapy to manage P. aeruginosa-mediated infections. Recently, the efficacy of phage therapy using a genetically modified filamentous phage (Pf3R) (10), lytic phage isolates or phage cocktails has been investigated against various experimental mouse infection models by P. aeruginosa that include burn wound infection (23) and gut-derived sepsis (37). Because the pathophysiology caused by P. aeruginosa infections is quite complicated, more and more relevant infection models need to be tested for the efficacy and relevancy of the antibacterial therapies.
The above information disclosed in this Background section is only for enhancement of understanding of the background of the invention and therefore it may contain information that does not form the prior art that is already known in this country to a person of ordinary skill in the art.
Throughout this application, various publications and patents are referred and citations are provided in parentheses. The disclosures of these publications and patents in their entities are hereby incorporated by references into this application in order to fully describe this invention and the state of the art to which this invention pertains.